chr16-68834619-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004360.5(CDH1):c.*1120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 241,904 control chromosomes in the GnomAD database, including 3,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.18 ( 2356 hom., cov: 32)
Exomes 𝑓: 0.17 ( 1398 hom. )
Consequence
CDH1
NM_004360.5 3_prime_UTR
NM_004360.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.682
Genes affected
CDH1 (HGNC:1748): (cadherin 1) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 16-68834619-T-C is Benign according to our data. Variant chr16-68834619-T-C is described in ClinVar as [Benign]. Clinvar id is 320291.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.*1120T>C | 3_prime_UTR_variant | 16/16 | ENST00000261769.10 | ||
CDH1 | NM_001317184.2 | c.*1120T>C | 3_prime_UTR_variant | 15/15 | |||
CDH1 | NM_001317185.2 | c.*1120T>C | 3_prime_UTR_variant | 16/16 | |||
CDH1 | NM_001317186.2 | c.*1120T>C | 3_prime_UTR_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.*1120T>C | 3_prime_UTR_variant | 16/16 | 1 | NM_004360.5 | P1 | ||
CDH1 | ENST00000566612.5 | c.*2009T>C | 3_prime_UTR_variant, NMD_transcript_variant | 15/15 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.178 AC: 27019AN: 152114Hom.: 2351 Cov.: 32
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GnomAD4 exome AF: 0.170 AC: 15218AN: 89672Hom.: 1398 Cov.: 0 AF XY: 0.168 AC XY: 7101AN XY: 42196
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
CDH1-related diffuse gastric and lobular breast cancer syndrome Benign:1
Benign, reviewed by expert panel | curation | ClinGen CDH1 Variant Curation Expert Panel | Aug 10, 2023 | The NM_004360.5(CDH1):c.*1120T>C variant has an allele frequency of 0.21013 (21%, 730/3474 alleles, 79 homozygotes) in the African subpopulation of the gnomAD v2.1.1 cohort (BA1; BP2). Therefore, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1, BP2. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at